Project Summary/Abstract The Pathology Core provides pathology and laboratory support for all SPORE projects including collection, prioritization, distribution and interrogation of both human prostate tissue and mouse models of prostate cancer (PCa). The Core collects and annotates diverse specimens, including fresh, frozen and formalin-fixed human tissue, biopsies including surveillance biopsies. The Core constructs tissue mircroarrays, processes whole mount and regular tissue blocks and tissue sections, and collects serum, plasma and urine for the analysis of DNA, RNA and protein. All specimens are collected at UCLA, Cedars-Sinai Medical Center (CSMC) and Greater LA VA Medical Center (GLA VA) in accordance with institutional guidelines and following established protocols with informed consent and patient confidentiality protected. Biospecimen repositories and data resources from the 3 sites are virtually integrated into a single unit. Through database infrastructure, collected bio-materials are linked to the clinical database at the parent institution and virtually integrated so that pathological, clinical, and family history data are available across institutions to maximize their potential use in translational research. Finally, the Pathology Core is responsible for prioritizing the access to all Core materials, with preference given to SPORE investigators. The Pathology Core is fully integrated with the Jonsson Cancer Center translational pathology core laboratory to avoid duplication of services and consolidate resources. Integrative services include enumeration and characterization of circulating tumor cells (CTCs) in a novel nanotechnology-based platform co-developed by the core, preparation of live epithelial cells from fresh human prostate tissue, laser-capture microdissection, digital pathology, quantitative immunohistochemistry (IHC) and immunofluorescence (IF) as well as multiplex immunohistochemistry. The core uses whole mount sections to correlate pathologic findings with imaging studies. Several specialized techniques to increase the knowledge gained from tissues are provided by the Core, such as multiplex immunohistochemical localization of proteins and RNA, laser capture microscopy, 3- dimensional visualization of cells in tissues through tissue clearing and light-sheet microscopy and computerized digital image analysis to quantify the cellular content and tissue architecture in pathology slides. In this context, the Pathology Core has the capacity to generate datasets from hematoxylin and eosin (H&E) and IHC/IF slides using whole slide digital scanning with machine learning and deep learning pipelines. The resulting data format is well suited for integration with other ?OMICS? data (i.e. genomics, proteomics, etc.). The large repertoire of available services is tailored to support each individual project or career development award. The Pathology Core has heavily invested in developing and acquiring new technologies to solve problems related to the procurement and analysis of all pathological specimens.